The effect of donor against recipient one-way HLA mismatch on liver transplantation outcomes from a multicenter registry analysis.

Donor against recipient one-way Human leukocyte antigen (HLA) mismatch (D → R one-way HLA MM) seemed strongly associated with graft-versus-host disease (GVHD). The aim of this study is to investigate the relevance of D → R one-way HLA MM in outcome of liver transplantation (LT). We retrospectively analyzed 2670 patients in Korean Organ Transplantation Registry database between April 2014 and December 2020. The patients were categorized into two groups whether D → R one-way HLA MM or not and evaluated the outcomes of LT between the two groups. 18 patients were found to be D → R one-way HLA MM. The incidence of GVHD (0.3% vs. 22.2%, p < 0.001) and mortality rate (11.6% vs. 38.9%, p = 0.003) was much higher in D → R one-way HLA MM group. D → R one-way HLA MM at 3 loci was seemed to be strongly associated with the incidence of GVHD (OR 163.3, p < 0.001), and found to be the strongest risk factor for patient death (HR 12.75, p < 0.001). Patients with D → R one-way HLA MM at 3 loci showed significantly lower overall survival (p < 0.001) but there were no significant differences in rejection-free survival and death-censored graft survival. D → R one-way HLA MM at 3 loci not only affects the overall survival of LT patients but also the incidence of GVHD.

Physical Performance Decline During the Early Posttransplantation Period Affects Survival After Living Donor Liver Transplantation.

BACKGROUND: Patient physical performance has been emphasized in liver transplant recipients; however, evidence for living donor liver transplantation (LDLT) patients is lacking. This study investigated the impact of physical performance decline during the early posttransplantation period on survival and risk factors for this decline in LDLT recipients. METHODS: From national registry data, 2703 LDLT patients were divided into 2 groups based on the change in their Karnofsky performance status (KPS) between 1 and 6 mo posttransplantation: declined KPS (n = 188) and control (n = 2515). Multivariable analyses were conducted to control for confounders, including posttransplantation complications. RESULTS: Estimated 5-y patient survival rates were 91.6% in the declined KPS group and 96.3% in the control group, favoring the latter ( P = 0.003). The survival hazard of KPS decline was significant in a baseline covariates-adjusted Cox model (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.37-4.95) and an adjusted model accounting for posttransplantation complications (HR, 3.38; 95% CI, 1.70-6.72). In subgroup analyses, KPS decline independently reduced survival in patients without complications (HR, 3.95; 95% CI, 1.67-9.34), and the trend was similar in patients with complications, although significance was marginal (HR, 3.02; 95% CI, 0.98-9.27). We found that only posttransplantation complications, such as rejection, infection, bile duct complication, and vascular complication, were significant risk factors for KPS decline after LDLT. CONCLUSIONS: Physical performance decline during the early posttransplantation period independently reduced survival rates, and posttransplantation complications were the only significant risk factors for physical performance decline in LDLT recipients.

Modified non-flared fully covered self-expandable metal stent for preoperative biliary drainage in pancreatic cancer.

BACKGROUND AND AIM: Durable biliary drainage is essential in patients with pancreatic cancer in the era of effective neoadjuvant chemotherapy (NACT). Plastic stent (PS) tends to occlude easily, and current metal stents are designed for nonresectable cancer. We evaluated the efficacy of a modified non-flared fully covered self-expandable metal stent (M-FCSEMS) during the perioperative period in patients with resectable or borderline resectable pancreatic cancer. METHODS: Consecutive patients with resectable or borderline resectable pancreatic ductal adenocarcinoma had a 12-mm M-FCSEMS (M-FCSEMS group) or 7-Fr PS (PS group) placed for biliary decompression before NACT or curative-intent surgery. The primary outcome was the re-intervention rate, and secondary outcomes were technical success, stent patency, and adverse events (AEs). RESULTS: Endoscopic stent placement was technically successful in all 60 patients. Twenty-three patients underwent surgery and 37 NACT before surgery. Re-intervention was performed in 10.0% (3/30) of patients in the M-FCSEMS group and 36.7% (11/30) of patients in the PS group (P = 0.030). The stent patency at 180 days was 89.8% (95% confidence interval, 77.3-100.0%) in the M-FCSEMS group and 30.2% (95% confidence interval, 11.4-80.0%) in the PS group (P < 0.0001). Stent-related AEs occurred in 10.0% (3/30) in the M-FCSEMS group and 40.0% (12/30) in the PS group (P = 0.015). Surgery-related AEs occurred in 10.5% (2/19) and 14.3% (3/21) in the M-FCSEMS and PS groups (P = 0.549). CONCLUSIONS: Modified non-flared fully covered self-expandable metal stents are effective and safe for durable biliary drainage in patients with resectable or borderline resectable pancreatic cancer during the perioperative period.

Investigating the spatio-temporal variation of hepatitis A in Korea using a Bayesian model.

Hepatitis A is a water-borne infectious disease that frequently occurs in unsanitary environments. However, paradoxically, those who have spent their infancy in a sanitary environment are more susceptible to hepatitis A because they do not have the opportunity to acquire natural immunity. In Korea, hepatitis A is prevalent because of the distribution of uncooked seafood, especially during hot and humid summers. In general, the transmission of hepatitis A is known to be dynamically affected by socioeconomic, environmental, and weather-related factors and is heterogeneous in time and space. In this study, we aimed to investigate the spatio-temporal variation of hepatitis A and the effects of socioeconomic and weather-related factors in Korea using a flexible spatio-temporal model. We propose a Bayesian Poisson regression model coupled with spatio-temporal variability to estimate the effects of risk factors. We used weekly hepatitis A incidence data across 250 districts in Korea from 2016 to 2019. We found spatial and temporal autocorrelations of hepatitis A indicating that the spatial distribution of hepatitis A varied dynamically over time. From the estimation results, we noticed that the districts with large proportions of males and foreigners correspond to higher incidences. The average temperature was positively correlated with the incidence, which is in agreement with other studies showing that the incidences in Korea are noticeable in spring and summer due to the increased outdoor activity and intake of stale seafood. To the best of our knowledge, this study is the first to suggest a spatio-temporal model for hepatitis A across the entirety of Korean. The proposed model could be useful for predicting, preventing, and controlling the spread of hepatitis A.

Field-induced quantum spin disordered state in spin-1/2 honeycomb magnet Na2Co2TeO6.

Spin-orbit coupled honeycomb magnets with the Kitaev interaction have received a lot of attention due to their potential of hosting exotic quantum states including quantum spin liquids. Thus far, the most studied Kitaev systems are 4d/5d-based honeycomb magnets. Recent theoretical studies predicted that 3d-based honeycomb magnets, including Na2Co2TeO6 (NCTO), could also be a potential Kitaev system. Here, we have used a combination of heat capacity, magnetization, electron spin resonance measurements alongside inelastic neutron scattering (INS) to study NCTO's quantum magnetism, and we have found a field-induced spin disordered state in an applied magnetic field range of 7.5 T < B (⊥ b-axis) < 10.5 T. The INS spectra were also simulated to tentatively extract the exchange interactions. As a 3d-magnet with a field-induced disordered state on an effective spin-1/2 honeycomb lattice, NCTO expands the Kitaev model to 3d compounds, promoting further interests on the spin-orbital effect in quantum magnets.

Antiferromagnetic Kitaev interaction inJeff=1/2 cobalt honeycomb materials Na3Co2SbO6and Na2Co2TeO6.

Finding new materials with antiferromagnetic (AFM) Kitaev interaction is an urgent issue for quantum magnetism research. We conclude that Na3Co2SbO6and Na2Co2TeO6are new honeycomb cobalt-based systems with AFM Kitaev interaction by carrying out inelastic neutron scattering experiments and subsequent analysis. The spin-orbit excitons observed at 20-28 meV in both compounds strongly support the idea that Co2+ions of both compounds have a spin-orbital entangledJeff= 1/2 state. Furthermore, we found that a generalized Kitaev-Heisenberg Hamiltonian can describe the spin-wave excitations of both compounds with additional 3rd nearest-neighbor interaction. Our best-fit parameters show significant AFM Kitaev terms and off-diagonal symmetric anisotropy terms of a similar magnitude in both compounds. We also found a strong magnon-damping effect at the higher energy part of the spin waves, entirely consistent with observations in other Kitaev magnets. Our work suggests Na3Co2SbO6and Na2Co2TeO6as rare examples of the AFM Kitaev magnets based on the systematic studies of the spin waves and analysis.

Spin texture induced by non-magnetic doping and spin dynamics in 2D triangular lattice antiferromagnet h-Y(Mn,Al)O3.

Novel effects induced by nonmagnetic impurities in frustrated magnets and quantum spin liquid represent a highly nontrivial and interesting problem. A theoretical proposal of extended modulated spin structures induced by doping of such magnets, distinct from the well-known skyrmions has attracted significant interest. Here, we demonstrate that nonmagnetic impurities can produce such extended spin structures in h-YMnO3, a triangular antiferromagnet with noncollinear magnetic order. Using inelastic neutron scattering (INS), we measured the full dynamical structure factor in Al-doped h-YMnO3 and confirmed the presence of magnon damping with a clear momentum dependence. Our theoretical calculations can reproduce the key features of the INS data, supporting the formation of the proposed spin textures. As such, our study provides the first experimental confirmation of the impurity-induced spin textures. It offers new insights and understanding of the impurity effects in a broad class of noncollinear magnetic systems.

Differences in Bile Microbiology and Antibiotic Resistances between Liver Transplant Recipients and Non-Transplant Patients.

Background: Treatment of biliary infection in liver transplant (LT) recipients is a challenge, especially because of ineffectiveness of the antibiotic agents otherwise recommended for non-transplant populations. We aimed to understand the factors underlying the choice of antibiotic therapy. Patients and Methods: A total of 373 bile cultures from LT recipients with biliary complications (n = 127; LT group) and from a non-transplant population that underwent cholecystectomy for acute cholecystitis (n = 246; non-transplant group) between January 2009 and December 2018, were investigated. Results: Polymicrobial cultures (13.4% vs. 1.6%; p < 0.001), Enterococcus faecium (26.0% vs. 8.5%; p < 0.001), and Pseudomonas (13.4% vs. 4.1%; p = 0.001) in the LT group, and non-faecium enterococci (3.9% vs. 18.3%; p < 0.001) and Enterobacteriales (40.2% vs. 54.9%; p = 0.007), especially Escherichia (11.0% vs. 29.7%; p < 0.001), in the non-transplant group, showed higher abundance. Most of the antibiotic agents recommended as initial antibiotic therapy for the non-transplant population as per previous guidelines were not effective in LT recipients. The incidences of Enterococcus faecium (14.9% vs. 32.5%; p = 0.029) in the LT recipients with model for end-stage liver disease (MELD) score >12 and non-faecium enterococci (8.5% vs. 1.3%; p = 0.042) in those with MELD score ≤12 were higher than those in the other group. The incidence of Enterobacteriales increased over time after LT (p = 0.048) and was similar to that in the non-transplant group after one year of LT. Bile micro-organisms in LT recipients, resistant to most antibiotic agents, especially soon after LT changed over time and became similar to those in the non-transplant group after one year of LT. Conclusions: Antibiotic therapy for biliary infection in LT recipients should be different from that in non-transplant populations, considering clinical factors such as the time interval after LT and MELD score.

Topological Magnon Band Crossing in Y_{2}Ir_{2}O_{7}.

Topological magnonic materials have attracted much interest because of the potential for dissipationless spintronic applications. Pyrochlore iridates are theoretically regarded as good candidates for designing topological magnon bands. However, experimental identification of topological magnon bands in pyrochlore iridates remains elusive. We explored this possibility in Y_{2}Ir_{2}O_{7} using Raman spectroscopy to measure both the single-magnon excitations and anomalous phonon shifts. From the single-magnon energies and tight-binding model calculations concerning the phonons, we determined the key parameters in the spin Hamiltonian. These confirm that Y_{2}Ir_{2}O_{7} hosts a nontrivial magnon band topology distinct from other pyrochlore iridate compounds. Our work demonstrates that pyrochlore iridates constitute a system in which the magnon band topology can be tailored and that Raman spectroscopy is a powerful technique to explore magnon band topology.

Magnetization Density Distribution of Sr_{2}IrO_{4}: Deviation from a Local j_{eff}=1/2 Picture.

5d iridium oxides are of huge interest due to the potential for new quantum states driven by strong spin-orbit coupling. The strontium iridate Sr_{2}IrO_{4} is particularly in the spotlight because of the so-called j_{eff}=1/2 state consisting of a quantum superposition of the three local t_{2g} orbitals with, in its simplest version, nearly equal populations, which stabilizes an unconventional Mott insulating state. Here, we report an anisotropic and aspherical magnetization density distribution measured by polarized neutron diffraction in a magnetic field up to 5 T at 4 K, which strongly deviates from a local j_{eff}=1/2 picture even when distortion-induced deviations from the equal weights of the orbital populations are taken into account. Once reconstructed by the maximum entropy method and multipole expansion model refinement, the magnetization density shows four cross-shaped positive lobes along the crystallographic tetragonal axes with a large spatial extent, showing that the xy orbital contribution is dominant. The analogy to the superconducting copper oxide systems might then be weaker than commonly thought.

Momentum-Dependent Magnon Lifetime in the Metallic Noncollinear Triangular Antiferromagnet CrB_{2}.

Noncollinear magnetic order arises for various reasons in several magnetic systems and exhibits interesting spin dynamics. Despite its ubiquitous presence, little is known of how magnons, otherwise stable quasiparticles, decay in these systems, particularly in metallic magnets. Using inelastic neutron scattering, we examine the magnetic excitation spectra in a metallic noncollinear antiferromagnet CrB_{2}, in which Cr atoms form a triangular lattice and display incommensurate magnetic order. Our data show intrinsic magnon damping and continuumlike excitations that cannot be explained by linear spin wave theory. The intrinsic magnon linewidth Γ(q,E_{q}) shows very unusual momentum dependence, which our analysis shows to originate from the combination of two-magnon decay and the Stoner continuum. By comparing the theoretical predictions with the experiments, we identify where in the momentum and energy space one of the two factors becomes more dominant. Our work constitutes a rare comprehensive study of the spin dynamics in metallic noncollinear antiferromagnets. It reveals, for the first time, definite experimental evidence of the higher-order effects in metallic antiferromagnets.

Solo single-incision laparoscopic cholecystectomy: a safe substitute for conventional laparoscopic cholecystectomy.

BACKGROUND: Despite the incremental application of single-incision laparoscopic cholecystectomy (SILC), this procedure has technical difficulties, including physical disturbance and an unstable surgical view through the small incision; therefore, we introduce the solo SILC (S-SILC) technique using a laparoscopic scope holder, as a simple, fixed and easy-to-perform procedure for an unassisted surgeon. METHODS: We performed a comparative analysis of S-SILC (n = 566) and conventional three-incision laparoscopic cholecystectomy (n = 874) performed from January 2013 to December 2016 at multiple centres. RESULTS: There was no significant difference of operative time between the two groups (P = 0.176); however, S-SILC showed a higher incidence of intraoperative gallbladder perforation, especially in the initial period (17.0% versus 2.3%, P < 0.001); and shorter post-operative hospital stay (3.3 ± 1.7 versus 1.9 ± 2.7 days, P < 0.001) than conventional three-incision laparoscopic cholecystectomy. There were no significant differences in major post-operative complications between the two groups (P = 0.909) and operation type (P = 0.971) was not a significant risk factor for major post-operative complications in multivariate analysis. CONCLUSION: S-SILC is a feasible and safe procedure; however, careful selection of surgical candidates is necessary in the early period of the experience with this method.

A Tailored Strategy for Recipient Hepatectomy: Left Portal Flow Preserving High Hilar Dissection.

BACKGROUND: Lee et al. (Liver Transpl 10(9):1158-1162, 2004) reported high hilar dissection (HHD) technique as a novel method for recipient hepatectomy to overcome limitations of conventional hilar dissection (CHD). HHD allowed performing multiple tension-free biliary anastomoses and easy reconstruction of double portal vein orifices. However, longer anhepatic phase is its main drawback. We describe a new modification of original HHD, called left portal vein flow preserving HHD (LFP-HHD). The new technique aims to gain the balance between CHD and original HHD. METHODS: The detailed technique of recipient hepatectomy by LFP-HHD is shown in the electronic video file. It involves high intrahepatic division of hilar structures while maintaining portal drainage through maintained left portal vein (LPV). Control of right hemi-liver inflow allows for division of right hepatic vein, and safe dissection of inferior vena cava (IVC) and hilar structures. According to coordination with donor surgery, the liver could be easily explanted. DISCUSSION: LFP-HHD has the same principle of original HHD allowing for multiple tension-free well-vascularized biliary anastomoses. LFP-HHD allows for shortening of anhepatic phase duration as portal venous drainage is continued through maintained LPV avoiding prolonged total portal clamping with bowel edema or the need for temporary porto-caval shunt. On the other hand, the number and the length of the hilar structures can be decreased compared with the original HHD technique. However, the level of division of the hilar structures is acceptable in most of the cases. CONCLUSION: LFP-HHD is a novel simple technique for recipient hepatectomy that can be tailored for certain clinical conditions.

Inhibitory effect of vitamin C on intrinsic aging in human dermal fibroblasts and hairless mice.

Vitamin C significantly reduced senescence-associated ß-galactosidase (SA-ß-gal) activity, with both the suppression of cell-cycle inhibitors (p53, p21, p16, and pRb) and stimulation of cell-cycle activators (E2F1 and E2F2). Vitamin C also effectively attenuated the hyperactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase-B (AKT) signaling pathway. The expression of the longevity marker, the mammalian target of rapamycin (mTOR), was down-regulated by vitamin C while the expressions of forkhead box O3a (FoxO3a) and sirtuin1 (SIRT1) were up-regulated by vitamin C. In the middle-aged (MA) mice, oral administration of vitamin C significantly inhibited wrinkle formation, skin atrophy, and loss of elasticity through increasing collagen and elastic fiber. The increase in transepidermal water loss and the decrease in skin hydration were recovered by vitamin C treatment in the MA mice. Overall, vitamin C effectively prevents cellular senescence in vitro and in vivo suggesting it has protective potential against natural aging of the skin.

Homeoprotein DLX4 expression is increased in inflammatory breast cancer cases from an urban African-American population.

Protein expression of Distal-less homeobox 4 (DLX4) was analyzed in inflammatory breast cancer (IBC) cases from an African-American (AA) population to determine if a) DLX4 gene over expression exists in this cohort and b) if the overexpression is associated with breast cancer clinicopathological characteristics (ER, PR, HER2, triple-negative). Twenty-nine blocks of formalin-fixed paraffin-embedded (FFPE) tissue from well-characterized human IBC cases were used for immunohistochemical staining (IHC). IHC results were assigned an intensity and percentage score. Percentage scores were assigned as 0, 1, 2, 3, or 4 and intensity scores were assigned 0, 1+, 2+ or 3+. For the analysis of the IHC, a percentage score of 3 or 4 and an intensity score of 2+ or 3+ were categorized as high. Chi-square or Fisher's exact tests were used to compare the high and low groups. In this cohort, 89.7% (26 out of 29) of IBC cases showed high percentages of positive cells staining for the DLX4 protein, while 40.0% (12 out of 30) of normal breast tissue from reduction mammoplasty cases demonstrated DLX4 expression (p < 0.01). In IBC patients, 65.5% of cases showed a high level of staining intensity, compared to 20.0% of normal breast tissues (test, p = 0.001). Intensity to DLX4 was higher in the HER2 negative status (78.3%) than the HER2 positive status (16.7%) (test, p = 0.011). DLX4 expression is higher in the IBC cases in this study of an urban AA population than in normal breast tissue cases. HER2 negative status is positively associated with high intensity of DLX4.

Low-energy spin dynamics of orthoferrites AFeO3 (A = Y, La, Bi).

YFeO3 and LaFeO3 are members of the rare-earth orthoferrites family with Pbnm space group. Using inelastic neutron scattering, the low-energy spin excitations have been measured around the magnetic Brillouin zone center. Splitting of magnon branches and finite magnon gaps (∼2 meV) are observed for both compounds, where the Dzyaloshinsky-Moriya interactions account for most of this gap with some additional contribution from single-ion anisotropy. We also make comparisons with multiferroic BiFeO3 (R3c space group), in which similar behavior was observed. By taking into account all relevant local Dzyaloshinsky-Moriya interactions, our analysis allows for the precise determination of all experimentally observed parameters in the spin-Hamiltonian. We find that different properties of the Pbnm and R3c space group lead to the stabilization of a spin cycloid structure in the latter case but not in the former, which explains the difference in the levels of complexity of magnon band structures for the respective compounds.

Giant thermal hysteresis in Verwey transition of single domain Fe3O4 nanoparticles.

Most interesting phenomena of condensed matter physics originate from interactions among different degrees of freedom, making it a very intriguing yet challenging question how certain ground states emerge from only a limited number of atoms in assembly. This is especially the case for strongly correlated electron systems with overwhelming complexity. The Verwey transition of Fe3O4 is a classic example of this category, of which the origin is still elusive 80 years after the first report. Here we report, for the first time, that the Verwey transition of Fe3O4 nanoparticles exhibits size-dependent thermal hysteresis in magnetization, 57Fe NMR, and XRD measurements. The hysteresis width passes a maximum of 11 K when the size is 120 nm while dropping to only 1 K for the bulk sample. This behavior is very similar to that of magnetic coercivity and the critical sizes of the hysteresis and the magnetic single domain are identical. We interpret it as a manifestation of charge ordering and spin ordering correlation in a single domain. This work paves a new way of undertaking researches in the vibrant field of strongly correlated electron physics combined with nanoscience.

Studies on the high-temperature ferroelectric transition of multiferroic hexagonal manganite RMnO3.

Hexagonal manganites are multiferroic materials with two highly-dissimilar phase transitions: a ferroelectric transition (from P63/mmc to P63cm) at a temperature higher than 1000 K and an antiferromagnetic transition at T N = 65-130 K. Despite its critical relevance to the intriguing ferroelectric domain physics, the details of the ferroelectric transition are not well known to date primarily because of the ultra-high transition temperature. Using high-temperature x-ray diffraction experiments, we show that the ferroelectric transition is a single transition of abrupt order and R-Op displacement is the primary order parameter. This structural transition is then simultaneously accompanied by MnO5 tilting and the subsequent development of electric polarization.

Time-reversal symmetry breaking hidden order in Sr2(Ir,Rh)O4.

Layered 5d transition iridium oxides, Sr2(Ir,Rh)O4, are described as unconventional Mott insulators with strong spin-orbit coupling. The undoped compound, Sr2IrO4, is a nearly ideal two-dimensional pseudospin-1/2 Heisenberg antiferromagnet, similarly to the insulating parent compound of high-temperature superconducting copper oxides. Using polarized neutron diffraction, we here report a hidden magnetic order in pure and doped Sr2(Ir,Rh)O4, distinct from the usual antiferromagnetic pseudospin ordering. We find that time-reversal symmetry is broken while the lattice translation invariance is preserved in the hidden order phase. The onset temperature matches that of the odd-parity hidden order recently highlighted using optical second-harmonic generation experiments. The novel magnetic order and broken symmetries can be explained by the loop-current model, previously predicted for the copper oxide superconductors.

Spherical Process Models for Global Spatial Statistics.

Statistical models used in geophysical, environmental, and climate science applications must reflect the curvature of the spatial domain in global data. Over the past few decades, statisticians have developed covariance models that capture the spatial and temporal behavior of these global data sets. Though the geodesic distance is the most natural metric for measuring distance on the surface of a sphere, mathematical limitations have compelled statisticians to use the chordal distance to compute the covariance matrix in many applications instead, which may cause physically unrealistic distortions. Therefore, covariance functions directly defined on a sphere using the geodesic distance are needed. We discuss the issues that arise when dealing with spherical data sets on a global scale and provide references to recent literature. We review the current approaches to building process models on spheres, including the differential operator, the stochastic partial differential equation, the kernel convolution, and the deformation approaches. We illustrate realizations obtained from Gaussian processes with different covariance structures and the use of isotropic and nonstationary covariance models through deformations and geographical indicators for global surface temperature data. To assess the suitability of each method, we compare their log-likelihood values and prediction scores, and we end with a discussion of related research problems.